Key populations within the generalized HIV epidemic in sub-Saharan Africa (SSA) have received insufficient attention including female sex workers (FSWs), a group with HIV prevalence substantially higher than the general population and a major contributor to the HIV epidemic in Kenya. Young FSWs (18-24 years old), a vulnerable population, are at highest risk among FSWs and require tailored biomedical, behavioral and structural interventions to counter the epidemiological and contextual complexities they face. We propose the IPrEP Research Project which includes: 1) formative research, inclusive of qualitative research among young FSWs, male clients (MCs) to elucidate life challenges, motivations and perceptions of HIV risks; risk behaviors; knowledge, attitudes about HIV and HIV prevention, including PrEP; preferences for adherence support; and sex partner relations. Interviews with health care providers (HCPs) will assess knowledge regarding HIV prevention and PrEP and attitudes towards FSWs; 2) an enhanced oral pre-exposure prophylaxis (PrEP) study among young FSWs to determine the uptake, adherence, feasibility and acceptability of combination strategy of PrEP, a biomedical intervention, with behavioral and structural adherence interventions (peer support versus reminders and resource transfer) and risk-reduction counseling intervention; 3) feasibility study for recruitment and retention of MCs with assessment of acceptability of risk-reduction counseling intervention; 4) cost-effectiveness analysis in collaboration with University of Nairobi (UoN) of the combination PrEP strategies to inform implementation and scale-up and 5) capacity building in implementation research for nurse faculty and students at UoN building on PEPFAR Nursing Education Partnership Initiative (NEPI) experience and infrastructure. The proposed research is distinguished by several innovations, including focus on young FSW, a population a high risk in a geographic HIV hotspot in Kenya, as well as on MCs and HCPs who play key roles in access by FSWs to prevention services and to prevention methods. The research includes implementation of theoretically- driven combination prevention strategies inclusive of biomedical, behavioral and structural interventions and an intervention aimed to decrease sexual risk compensation and risk behaviors; the assessment of HCPs' knowledge and attitudes regarding HIV prevention, including PrEP, and FSWs; cost-effectiveness analysis to inform implementation and scale-up within PEPFAR-supported programs, as well as a commitment to building capacity to design, implement and analyze findings from implementation studies working with nursing partner. The ultimate goal of our research is to identify how PrEP can be effectively implemented for this young population at substantial risk for HIV decreasing their risk of HIV acquisition, consequently diminishing the overall number of new HIV infections in Kenya and similar settings. Findings from this research will also inform PEPFAR as it aims to stem the spread of HIV through the effective use of evidence-based interventions.